In this application for a Mentored Clinical Scientist Development Award, Susan K. Schultz will obtain expertise in risk factors for tardive dyskinesia (TD). Unfortunately, TD is common in the neuroleptic-treated elderly with an estimated prevalence ranging from one third to as high as two thirds of this population. TD constitutes a growing problem in the nation and will only increase as the proportion of elderly continues to rise and neuroleptic medications remain widely used for various psychotic syndromes in aging. Dr. Schultz will map the progression and determinants of neuroleptic-induced movement disorders in the elderly. She will examine the impact of proposed risk factors (i.e. impaired phenylalanine metabolism and diabetes mellitus) in relationship to documented risk factors such as age and neuroleptic exposure. The candidate proposes a training and research program using the resources of a psychiatry department with a long history of research as well as a Mental Health Clinical Research Center devoted to the neurobiology of schizophrenia. While Dr. Schultz has training in schizophrenia research, she requires additional training in psychopharmacology, the neurobiology of movement disorders and the design of longitudinal investigations of multiple risk factors in geriatric subjects. This training will be integrated with a research project seeking: 1) To plot the course of TD in elderly patients 2) To examine whether phenylalanine-induced abnormal movements predict the development of TD 3) To determine whether impaired glucose tolerance also predicts TD and 4) To develop a model for understanding the relationship between these experimental risk factors and known risk factors of increasing age and neuroleptic exposure. These findings will lead to the development of a therapeutic model for early TD intervention such as controlled exposure to phenylalanine and implementation of an appropriate regimen to prevent/delay the onset of impaired glucose tolerance. This award would provide the candidate with the necessary background for further studies of factors influencing the onset of movement disorders in the elderly and may yield important information regarding preventive measures and therapeutic interventions for these disorders. This award will also provide the candidate with the background for ongoing research and funding leading to an independent research career.